Toxicological effects of areca nut and tobacco leaf extracts alone and in combination in mice

:This study investigated the toxicological interactions between tobacco leaf and areca nut extracts in mice, focusing on hepatic and systemic metabolic functions. Mice received tobacco extract, areca nut extract, or their combination for 14 days. Serum biochemical markers, hepatic function, lipid metabolism, antioxidant enzyme activities, inflammatory mediators, and liver histopathology were evaluated. Tobacco extract induced hepatocellular injury, Cyclooxygenase-2 (COX-2)-mediated inflammation, and impaired antioxidant defenses, whereas areca nut extract primarily disrupted hepatic lipid metabolism. Combined exposure partially alleviated tobacco-induced toxicity, with aspartate aminotransferase (AST), direct bilirubin (DBIL), and blood urea nitrogen (BUN) approaching control levels, reduced hepatic lipid vacuolization through modulation of fatty acid synthase (FASN) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and attenuated inflammatory infiltration. Semi-quantitative histopathological scoring confirmed significantly lower liver injury in the combined exposure group than in the tobacco group. However, antioxidant capacity remained impaired, as indicated by decreased SOD, CAT, and GSH-Px activities and elevated MDA levels, suggesting persistent oxidative stress. These findings demonstrate distinct yet interactive toxicological effects of tobacco and areca nut extracts, providing new mechanistic insights into their combined biological impacts and informing future toxicological studies.